| First Author | Derecki NC | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 5 | Pages | 1067-80 |
| PubMed ID | 20439540 | Mgi Jnum | J:160932 |
| Mgi Id | MGI:4456322 | Doi | 10.1084/jem.20091419 |
| Citation | Derecki NC, et al. (2010) Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 207(5):1067-80 |
| abstractText | Proinflammatory cytokines have been shown to impair cognition; consequently, immune activity in the central nervous system was considered detrimental to cognitive function. Unexpectedly, however, T cells were recently shown to support learning and memory, though the underlying mechanism was unclear. We show that one of the steps in the cascade of T cell-based support of learning and memory takes place in the meningeal spaces. Performance of cognitive tasks led to accumulation of IL-4-producing T cells in the meninges. Depletion of T cells from meningeal spaces skewed meningeal myeloid cells toward a proinflammatory phenotype. T cell-derived IL-4 was critical, as IL-4(-/-) mice exhibited a skewed proinflammatory meningeal myeloid cell phenotype and cognitive deficits. Transplantation of IL-4(-/-) bone marrow into irradiated wild-type recipients also resulted in cognitive impairment and proinflammatory skew. Moreover, adoptive transfer of T cells from wild-type into IL-4(-/-) mice reversed cognitive impairment and attenuated the proinflammatory character of meningeal myeloid cells. Our results point to a critical role for T cell-derived IL-4 in the regulation of cognitive function through meningeal myeloid cell phenotype and brain-derived neurotrophic factor expression. These findings might lead to the development of new immune-based therapies for cognitive impairment associated with immune decline. |
